This proposal is concerned with a request to secure funds for a collaborative, interdisciplinary program to devise methods for the synthesis of novel structures, closely related to the ansamycins. Our objective is to develop derivatives and analogs that will be potent antiviral and antibacterial agents, not susceptible to cross resistance effects. The biosynthesis of the ansamycins will be studied using conventional C14 techniques and C13 labelled precursors in conjunction with C13-NMR, to determine the origin of the aromatic ring system the origin of the "ansa" bridge and their biosynthetic relationships. It is expected that knowledged derived from this study will be extremely useful in developing partial biosynthetic routes to novel ansamycin antibiotics. Ansamycins will also be modified chemically by the introduction of reactive functional groups, capable of forming covalent bonds to receptor proteins.